CRISPRi-mediated silencing of the ABC transporter Ms_5779 compromises cell envelope integrity and impairs intracellular host lipid exploitation

BackgroundMultidrug-resistant Mycobacterium tuberculosis (MDR-TB) poses a severe global health threat, yet the contribution of cell envelope barriers to intrinsic drug tolerance remains poorly understood. The ABC protein Rv0820 is conserved across mycobacteria but functionally uncharacterized, presenting a structural paradox: it lacks canonical transmembrane helices, making conventional efflux pump function mechanistically implausible.MethodsUsing CRISPR interference (CRISPRi), we silenced Ms_57